Nitrogen → 2-(2-Chloro-5-isopropenyl-pyridin-4-ylamino)-N-methyl-benzamide

HRID 62516Notes

Reaction equation

HRID 62516 reaction equation
N#N.Br[C:4]1[C:5]([NH:11][C:12]2[CH:21]=[CH:20][CH:19]=[CH:18][C:13]=2[C:14]([NH:16][CH3:17])=[O:15])=[CH:6][C:7]([Cl:10])=[N:8][CH:9]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[C:30]1(C)[CH:35]=CC=C[CH:31]=1>O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:10][C:7]1[CH:6]=[C:5]([NH:11][C:12]2[CH:21]=[CH:20][CH:19]=[CH:18][C:13]=2[C:14]([NH:16][CH3:17])=[O:15])[C:4]([C:30]([CH3:35])=[CH2:31])=[CH:9][N:8]=1

Participants

7

Reactant 4

HCID 947NitrogenHCID 1140TolueneHCID 62657Potassium Phosphate, TribasicHCID 575169042-[(5-Bromo-2-chloro-4-pyridinyl)amino]-N-methylbenzamide

Product 1

HCID 575169072-(2-Chloro-5-isopropenyl-pyridin-4-ylamino)-N-methyl-benzamide

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent

Conditions

Temperature
110 °C

Procedure

In a tube a solution of isopropenyboronic acid pinacol ester (3.31 mL, 17.6 mmole, 3 eq) in toluene (200 mL) was degassed with N2 at 50° C. for 15 min. To this was added Pd(PPh3)4 (0.68 g, 0.59 mmole, 0.1 eq) and 2-(5-bromo-2-chloro-pyridin-4-ylamino)-N-methyl-benzamide (2 g, 5.87 mmole, 1 eq). This mixture was again degassed with N2 for 30 min. A degassed solution of K3PO4 (4.98 g, 23.48 mmole, 4 eq) in H2O (8 mL) was added to the above mixture in one portion and the resulting mixture was heated at 110° C. for overnight. After completion of the reaction, it was allowed to cool to room temperature and solvent was removed under reduced pressure to yield crude product. It was purified by column chromatography over silica gel (60-120 mesh) using 0.5% MeOH-DCM as the eluant to give the title compound as an off white solid (0.8 g, 45%). 1H-NMR (400 MHz, DMSO-d6): δ 2.06 (s, 3H), 2.73-2.74 (d, 3H, J=4.52 Hz), 5.14 (s, 1H), 5.46 (s, 1H), 7.04-7.15 (m, 2H), 7.45-7.60 (m, 2H), 7.64-7.71 (m, 1H), 7.96 (s, 1H), 8.60-8.72 (brs, 1H), 9.87 (s, 1H). LC-MS [M+H]+=302.2.

Workup

  1. customThis mixture was again degassed with N2 for 30 min
  2. customAfter completion of the reaction, it
  3. temperatureto cool to room temperature
  4. customsolvent was removed under reduced pressure
  5. customto yield crude product
  6. customIt was purified by column chromatography over silica gel (60-120 mesh)

Sources & evidence

ORD record
ord-69b4e772eb31435f9756ed06b045174c
Source dataset
uspto-grants-2016_09
Patent number
US09446034B2

Reaction notes

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